Official Title

Summary:

RATIONALE: Drugs used in chemotherapy, such as capecitabine, fluorouracil, and oxaliplatin
work in different ways to stop tumour cells from dividing so they stop growing or die.
Radiation therapy uses high-energy x-rays to damage tumor cells.
PURPOSE: This randomized phase III trial is studying radiation therapy and either
capecitabine or fluorouracil with or without oxaliplatin and comparing them to see how well
they work when given before surgery in treating patients with resectable rectal cancer. It
is not yet known whether radiation therapy and either capecitabine or fluorouracil is more
effective with or without oxaliplatin in treating rectal cancer.

Trial Description

Primary Outcome:

Loco-regional disease control as assessed by evidence of tumour at 3 years

Secondary Outcome:

Clinical complete response as assessed by digital rectal exam and sigmoidoscopy or proctoscopy at time of definitive analysis

Pathologic complete response as assessed by gross and microscopic exam of surgical specimens at time of definitive analysis

Sphincter-saving surgery at time of definitive analysis

Survival as measured by deaths from any cause at time of definitive analysis

Disease-free survival as assessed by recurrence, second primary cancer, or death from any cause at time of definitive analysis

Tissue biomarkers as assessed by analysis of tumor tissue using current biotechnology after definitive analysis

Quality of life as assessed by FACT-C trial outcome index and EORTC CR38 after definitive analysis

Neurotoxicity as assessed by FACT-NTX scale after definitive analysis

Symptoms as assessed by fluoropyrimidine symptom scale adapted from SWOG after definitive analysis

Vitality as assessed by SF-36 vitality scale after definitive analysis

Convenience of care as assessed by NSABP C-06 convenience of care scale adapted from ECOG after definitive analysis

OBJECTIVES:

Primary

Compare the rate of local-regional relapse in
patients with resectable rectal cancer treated with chemoradiotherapy comprising
radiation therapy and either capecitabine or fluorouracil with or without
oxaliplatin.

Secondary

Compare the rate of clinical complete response in
patients treated with these regimens.

Compare the rate of pathologic complete response
in patients treated with these regimens.

Determine the increase in the number of patients
who are able to undergo sphincter-saving surgery after treatment with these
regimens.

Correlate genetic patterns and the presence or
absence of specific tissue biomarkers with response and prognosis in patients
treated with these regimens.

Arm IV: Patients receive capecitabine and undergo
radiotherapy as in arm III. Patients also receive oxaliplatin as in arm
II.

Within 6-8 weeks after the
completion of chemoradiotherapy, patients with responding or stable disease
undergo surgery. Patients with progressive disease are treated at the discretion
of the investigator and continue to be followed.

Quality of life is assessed at
baseline, at completion of chemoradiotherapy, and at 1 year after surgery.

After completion of study
treatment, patients are followed every 6 months for 5 years.